Table 1 Summary of the clinical and molecular features of individuals with SMARCA1 variants
Family / Individual | Sex | Age | SMARCA1 variant | Inheritance | Macrocephaly | Motor delay | Speech delay1 | ID | Behavioral issues | Dysmorphic facial features2 | Other notable features & other molecular findings 3 |
|---|---|---|---|---|---|---|---|---|---|---|---|
Family 1 (DB17-332) (vi1) | M | 12y4m | c.271 C > T, p.Arg91* | Maternal | OFC + 6 SD | – | + (no language) | + (severe) | ASD | + (subtle) | Hydrocephalus s/p shunting, hepatosplenomegaly, overgrowth (height and weight +5 SD) |
Family 1 (DB17-332) (vi2) | M | 8 y | c.271 C > T, p.Arg91* | Maternal | OFC + 4.3 SD | – | + | + (mild) | – | – | Hydrocephalus (shunting not required), Splenomegaly, overgrowth (height + 3 SD, weight +3.7 SD) |
Family 1 (DB17-332) (vi8) | F | 14y7m | c.271 C > T, p.Arg91* | Maternal | OFC + 4.9 SD | – | – | Mild LD | – | + (subtle) | Severe obesity (BMI 50 kg/m2), normal brain MRI |
Family 1 (DB17-332) (vi9) | M | 8y9m | c.271 C > T, p.Arg91* | Maternal | OFC + 5.5 SD | – | – | Mild LD | – | + (subtle) | Obesity (BMI 24 kg/m2), normal Brain MRI |
Family 1 (DB17-332) (v2) | F | 45 y | c.271 C > T, p.Arg91* | Obligate Carrier | OFC + 1 SD | – | – | – | – | – | – |
Family 1 (DB17-332) (v10) | F | 49 y | c.271 C > T, p.Arg91* | Obligate Carrier | OFC + 1.5 SD | – | – | – | – | – | – |
Family 2 (DB20-184) | M | 6 y | c.271 C > T, p.Arg91* | Maternal | Macrocephaly | + | + | + | ASD, ADHD + | + (subtle) | – |
Family 3 (DB18-477) | F | 20 y | c.353 C > T, p.Thr118Ile | De novo | OFC + 3.4 SD | + | + | + | ASD | + | Epilepsy |
Family 4 (DB21-072) | M | 5.5 y | c.407 A > G, p.Gln136Arg | Maternal | OFC + 0.2 SD | + | + | + | ASD | + | – |
Family 5 (DB19-133) | F | 5 y | c.543dupG, p.Pro182Alafs*18 | ND | OFC + 3.3 SD | + | + | + | ASD + | – | Epilepsy, constipation, obesity, brother has ASD, epilepsy, hydrocephalus |
Family 6 (DB21-045) | M | 5 y | c.565 C > T, p.Arg189* | De novo | OFC + 5.6 SD | + | + | + | ADHD + | + | Hydrocephalus, pyloric stenosis No other relevant molecular findings |
Family 7 (DB22-086) | M | 11 y | c.566 G > A, p.Arg189Gln | De novo | OFC + 0.6 SD | – | + | – | + | + | Hepatosplenomegaly, accessory spleen, cleft palate |
Family 8 (DB22-096) | M | 12 y | c.685 C > T, p.Arg229* | ND/Presumably maternal | OFC + 7.6 SD | – | + | – | – | – | Tall stature, obesity, brother has similar clinical phenotype but not tested. |
Family 9 (DB20-175) | M | 4y4m | c.757 C > T, p.Arg253* | Maternal | OFC + 5.9 SD | – | + | + mild | – | + | Tall stature |
Family 9 (DB20-175) | F | 7y4m | c.757 C > T, p.Arg253* | Maternal | OFC –0.4 SD | + | + | + | + | + | Severe vision issues, feeding difficulties, laryngeal palsy, facial palsy, much more severely affected than brother |
Family 9 (DB20-175) (mother) | F | 43 y | c.757 C > T, p.Arg253* | Obligate Carrier | OFC + 5.6 SD | ND | _ | Mild LD | _ | _ | Tall stature |
Family 10 (DB20-204) | M | 5y10m | c.775 C > G, p.Arg259Gly | Maternal | OFC + 0.3 SD | + | + | + | + | + | Constipation |
Family 11 (DB19-123) | M | 14 y | c.916 C > T, p.Arg306* | Maternal | OFC + 4.1 SD | + | + | + | – | + (subtle) | – |
Family 12 (DB22-008) | M | 15 y | c.1070 T > G, p.Leu357* | Maternal | OFC + 0.1 SD | + | + | + | ASD, ADHD | + | Epilepsy |
Family 12 (DB22-008) | F | 18 y | c.1070 T > G, p.Leu357* | Maternal | OFC –0.8 SD | + | + | + (mild) | + | + | Epilepsy |
Family 13 (DB20-114) | M | 9 y | c.1071dupA, p.Leu358Ilefs*3 | Maternal | OFC > +2 SD | + | + | + | ASD, ADHD | – | Hirschsprung disease, Crohn’s disease |
Family 14 (DB21-09) | M | 5y7m | c.1295 T > C, p.Met432Thr | Maternal | OFC –0.3 SD | – | + | – | ASD + | – | – |
Family 14 (DB21-09) | M | 4y5m | c.1295 T > C, p.Met432Thr | Maternal | OFC + 0.5 SD | – | + | – | ASD + | – | – |
Family 15 (DB19-128) | M | 2y4m | c.1514 T > C, p. Val505Ala | Maternal | OFC normal by report | + | + | + | – | + | Epilepsy |
Family 16 (DB20-111) | F | 5 y | c.1680 T > A, p.Phe560Leu | De novo | OFC normal by report | – | + | + | + defiant | – | Epilepsy |
Family 17 (DB22-103) | M | 24 y | c.1940T>C, p.Ile647Thr | Maternal | ND | + | + | + | – | – | Epilepsy, family history of OTC deficiency |
Family 18 (DB24-075) | M | 12y7m | c.1971dup, p.Asn658* | ND/Presumably maternal | OFC + 2.4 | + | + | + | – | – | – |
Family 19 (DB19-232) | M | 5 y | c.2161 G > A, p.Asp721Asn | Maternal | OFC –0.2 SD | + | + | + | – | – | Epilepsy, cortical blindness |
Family 20 (DB22-081) | M | 9y11m | c.2252 G > A, p.Arg751Gln | ND/Presumably maternal | OFC + 0.9 SD | + | + | + | + | + | Short stature, sibs have similar features by report |
Family 21 (DB19-124) | M | 7 y | c.2311 G > A, p.Glu771Lys | Maternal | OFC + .25 SD | + | – | – | – | – | – |
Family 22 (DB19-127) | M | 4 y | c.2471 C > T, p.Pro824Leu | Maternal | OFC + 2.5 SD | + | + | + | ASD + | – | Congenital hydronephrosis. 9 y sister heterozygous with h/o dev delay, hypotonia, single kidney, joint hypermobility, and learning difficulties. 13 y sister with Greig cephalopolysyndactyly syndrome and heterozygous for SMARCA1 variant. |
Family 23 (DB22-041) | M | 10y7m | c.2681 A > T, p.Glu894Val | Maternal | OFC + 0.83 SD | – | + | – | ASD, ADHD + | – | – |
Family 24 (DB20-059) | M | 5 y | c.3007 T > C, p.Phe1003Leu | Maternal | OFC + 4.9 SD | + | + | + | – | + | – |
Family 25 (DB22-040) | M | 4y11m | c.3103_3106del, p.Arg1035Glnfs*13 | Maternal | OFC –1.2 SD | + | + | + | – | + | – |
Family 26 (DB19-380) | M | 13 y | c.3152 C > T, p.Ser1039Leu | ND /Presumably maternal | OFC WNL | – | + | + | + | + | – |
Total | 26 M/9 F | 2y4m-49y | 25 unique variants | 17 maternal /4 de novo/ 5 ND | 17/35 OFC > 2 (49%) | 20/34 (59%) | 29/35 (83%) | 27/35 (77%) | 19/35 (54%); ASD 11/35 (31%) | 19/35 (54%) | 23/35 (63%); Epilepsy 8/35 (23%) |
